Reacción #85746

Ecuación de reacción

EtOAc Heptane

methyl magnesium bromide

(R,E)-2-methyl-N-(4-(trifluoromethoxy)benzylidene)propane-2-sulfinamide

→

(R)-2-methyl-N—((S)-1-(4-(trifluoromethoxy)phenyl)ethyl)propane-2-sulfinamide

Rendimiento 62.0%

Disolventes

Et2O

CH2Cl2

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato warm up to room temperature
2. 2
   workup.STIRRINGstirred additional 4 hrs
3. 3
   TemperaturaThe reaction mixture was cooled again to 0° C.
4. 4
   Otroquenched with the slow addition of a saturated NH4Cl solution
5. 5
   workup.ADDITIONThe by-phasic mixture was diluted with DCM and Water
6. 6
   Extracciónthe aqueous extracted with DCM two times
7. 7
   Lavadowashed with brine
8. 8
   Secadodried (Na2SO4)
9. 9
   Filtraciónfiltered
10. 10
    Concentraciónconcentrated to 11.5 g crude white solid

Procedimiento

To a solution of (R,E)-2-methyl-N-(4-(trifluoromethoxy)benzylidene)propane-2-sulfinamide (7.7 g, 26.3 mmol) in CH2Cl2 (150 mL), cooled to 0° C. (water/ice bath), under nitrogen, was added 3M methyl magnesium bromide (35 mL, 105 mmol) in Et2O. The reaction mixture was stirred at 0° C. for 30 min, then allowed to warm up to room temperature and stirred additional 4 hrs. The reaction mixture was cooled again to 0° C. and quenched with the slow addition of a saturated NH4Cl solution. The by-phasic mixture was diluted with DCM and Water and the aqueous extracted with DCM two times. The organic phases were combined, washed with brine, dried (Na2SO4), filtered and concentrated to 11.5 g crude white solid. Silica gel column chromatography (EtOAc/Heptane 0 to 30%) afforded (R)-2-methyl-N—((S)-1-(4-(trifluoromethoxy)phenyl)ethyl)propane-2-sulfinamide (5.08 g, 16.2 mmol, 62% yield) as a white crystalline solid. 1H NMR (400 MHz, CDCl3) δ 1.21 (s, 9H) 1.53 (d, J=6.70 Hz, 3H) 3.31 (d, J=2.74 Hz, 1H) 4.59 (qd, J=6.67, 3.37 Hz, 1H) 7.18 (d, J=8.02 Hz, 2H) 7.36 (d, J=8.66 Hz, 2H). LCMS m/z 310.2 (M+H)+, Rt 0.90 min.

Fuente